Model of Transcriptional Activation by MarA in Escherichia coli

We have developed a mathematical model of transcriptional activation by MarA in Escherichia coli, and used the model to analyze measurements of MarA-dependent activity of the marRAB, sodA, and micF promoters in mar-rob- cells. The model rationalizes an unexpected poor correlation between the mid-point of in vivo promoter activity profiles and in vitro equilibrium constants for MarA binding to promoter sequences. Analysis of the promoter activity data using the model yielded the following predictions regarding activation mechanisms: (1) MarA activation of the marRAB, sodA, and micF promoters involves a net acceleration of the kinetics of transitions after RNA polymerase binding, up to and including promoter escape and message elongation; (2) RNA polymerase binds to these promoters with nearly unit occupancy in the absence of MarA, making recruitment of polymerase an insignificant factor in activation of these promoters; and (3) instead of recruitment, activation of the micF promoter might involve a repulsion of polymerase combined with a large acceleration of the kinetics of polymerase activity. These predictions are consistent with published chromatin immunoprecipitation assays of interactions between polymerase and the E. coli chromosome. A lack of recruitment in transcriptional activation represents an exception to the textbook description of activation of bacterial sigma-70 promoters. However, use of accelerated polymerase kinetics instead of recruitment might confer a competitive advantage to E. coli by decreasing latency in gene regulation.Comment: 30 pages, 2 figure

Elements of the Perpetuation of Dependency in a Psychiatric Halfway House

Halfway houses are intended as helping institutions for those who are attempting to make the transition from institutionalized mental health facilities to autonomous living in the community. In spite of the manifest goal to produce independence for its residents, however, the halfway house contributes to patterns of dependency. In addition to the network nature of mental health care, we identify three dependency-perpetuating elements: role commitments, language, and mixed messages. These elements are analyzed as both social organizational and social psychological processes, and their implications are discussed

Theory and Applications of Robust Optimization

In this paper we survey the primary research, both theoretical and applied, in the area of Robust Optimization (RO). Our focus is on the computational attractiveness of RO approaches, as well as the modeling power and broad applicability of the methodology. In addition to surveying prominent theoretical results of RO, we also present some recent results linking RO to adaptable models for multi-stage decision-making problems. Finally, we highlight applications of RO across a wide spectrum of domains, including finance, statistics, learning, and various areas of engineering.Comment: 50 page

Incorporating Breast Cancer Recurrence Events Into Population-Based Cancer Registries Using Medical Claims: Cohort Study.

BACKGROUND: There is a need for automated approaches to incorporate information on cancer recurrence events into population-based cancer registries. OBJECTIVE: The aim of this study is to determine the accuracy of a novel data mining algorithm to extract information from linked registry and medical claims data on the occurrence and timing of second breast cancer events (SBCE). METHODS: We used supervised data from 3092 stage I and II breast cancer cases (with 394 recurrences), diagnosed between 1993 and 2006 inclusive, of patients at Kaiser Permanente Washington and cases in the Puget Sound Cancer Surveillance System. Our goal was to classify each month after primary treatment as pre- versus post-SBCE. The prediction feature set for a given month consisted of registry variables on disease and patient characteristics related to the primary breast cancer event, as well as features based on monthly counts of diagnosis and procedure codes for the current, prior, and future months. A month was classified as post-SBCE if the predicted probability exceeded a probability threshold (PT); the predicted time of the SBCE was taken to be the month of maximum increase in the predicted probability between adjacent months. RESULTS: The Kaplan-Meier net probability of SBCE was 0.25 at 14 years. The month-level receiver operating characteristic curve on test data (20% of the data set) had an area under the curve of 0.986. The person-level predictions (at a monthly PT of 0.5) had a sensitivity of 0.89, a specificity of 0.98, a positive predictive value of 0.85, and a negative predictive value of 0.98. The corresponding median difference between the observed and predicted months of recurrence was 0 and the mean difference was 0.04 months. CONCLUSIONS: Data mining of medical claims holds promise for the streamlining of cancer registry operations to feasibly collect information about second breast cancer events

Virological and Immunological Effects of Combination Antiretroviral Therapy with Zidovudine, Lamivudine, and Indinavir during Primary Human Immunodeficiency Virus Type 1 Infection

Forty-seven patients presenting with primary human immunodeficiency virus (HIV) infection were treated with zidovudine 200 mg 3 times a day, lamivudine 150 mg 2 times a day, and indinavir 800 mg 3 times a day for 1 year. From a mean pretreatment viral RNA level of 4.93 log10 copies/mL, the proportions of patients having <500 copies/mL at 24 and 52 weeks were 92.0% and 89.2%, respectively. For the 35 patients with data available at 24 and 52 weeks, the corresponding proportions for the <50 copies/mL analysis were 86.6% and 79.3%, respectively. The change in virus load was −2.19 and −2.41 log10 copies/mL at weeks 8 and 52, respectively. CD4 cell counts increased, from a mean of 546 cells/mm3, by 142 cells/mm3 at week 24 and by 210 cells/mm3 at week 52. Three patients discontinued the study because of drug-related toxicity. Six (12.8%) patients had adverse experiences associated with nephrolithiasis. Combination therapy with zidovudine, lamivudine, and indinavir during primary HIV infection results in a profound and sustained reduction in virus load with concurrent recovery of the CD4 cell populatio

METAREP: JCVI metagenomics reports—an open source tool for high-performance comparative metagenomics

Summary: JCVI Metagenomics Reports (METAREP) is a Web 2.0 application designed to help scientists analyze and compare annotated metagenomics datasets. It utilizes Solr/Lucene, a high-performance scalable search engine, to quickly query large data collections. Furthermore, users can use its SQL-like query syntax to filter and refine datasets. METAREP provides graphical summaries for top taxonomic and functional classifications as well as a GO, NCBI Taxonomy and KEGG Pathway Browser. Users can compare absolute and relative counts of multiple datasets at various functional and taxonomic levels. Advanced comparative features comprise statistical tests as well as multidimensional scaling, heatmap and hierarchical clustering plots. Summaries can be exported as tab-delimited files, publication quality plots in PDF format. A data management layer allows collaborative data analysis and result sharing